Why is Peyton Manning struggling?
I don't think you have to look much further than his 534 attempts through 12 games. 4 of Peyton's previous 12 seasons had less attempts than that.
That's on pace for 712 attempts! A mark that would smash Drew Bledsoe's record of 691. That pace isn't skewed by one high attempts game either, the biggest outlier from the 44.5 attempt per game average is week 2 against the Giants (26 attempts), the only game this season in which Peyton has thrown less than 36 passes.
All these attempts extra attempts come at a price.
Diminishing returns is a central concept in economics and it's easy to see the application to football. Unbalanced playcalling lets the defense focus in on what the offense tends to do. If you are throwing 40+ times a game, opposing defenses will spend the week scheming against the pass and run lots of pass packages on Sunday. Obviously this will reduce the effectiveness of your passing offense.
In the 4 games with the least attempts this season Peyton has 0 picks, while the 5 highest attempt games includes all 4 of his multi-pick games. The only game among those 5 that would be considered up to Peyton Manning's standard was the opener against the Texans where the unbalanced nature of the offense wasn't yet evident and the opposing pass D was horrendously bad.
The recent rough patch for Manning has come when it's clear the Colts plan to throw the ball 35-40 times in anything but a Colts blowout, and with Peyton following through on that plan to the tune of 148 attempts the last 3 weeks. It seems the Colts have managed to find a place where they need to put the ball in Peyton's hands less.